In vivo chromosomal behavior is dictated by the organization of genomic DNA at length scales ranging from nanometers to microns. At these disparate scales, the DNA conformation is influenced by a range of proteins that package, twist and disentangle the DNA double helix, leading to a complex hierarchical structure that remains undetermined. Thus, there is a critical need for methods of structural characterization of DNA that can accommodate complex environmental conditions over biologically relevant length scales. Based on multiscale molecular simulations, we report on the possibility of measuring supercoiling in complex environments using angular correlations of scattered X-rays resulting from X-ray free electron laser (xFEL) experiments. We recently demonstrated the observation of structural detail for solutions of randomly oriented metallic nanoparticles [D. Mendez et al., Philos. Trans. R. Soc. B360 (2014) 20130315]. Here, we argue, based on simulations, that correlated X-ray scattering (CXS) has the potential for measuring the distribution of DNA folds in complex environments, on the scale of a few persistence lengths.
